Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function

We have analyzed the functional activity of the p53 tumor suppressor in hum an T-cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant le vels of the p53 protein mere detected in both HTLV-2A and -2B virus-infecte d cell lines. The p53 was functionally inactive, however, both in transient -transfection assays using a p53 reporter plasmid and in induction of p53-r esponsive genes in response to gamma irradiation. We further investigated H TLV-ZA Tax and HTLV-2B Tax effects on p53 activity, interestingly, although Tax-2A and -2B inactivate p53, the Tax-2A protein appears to inhibit p53 f unction less efficiently than either Tax-1 or Tax-2B. In transient-cotransf ection assays, Tax-1 and Tax-2B inactivated p53 by 80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-ZA does not increase the steady-stat e level of cellular p53 as well as Tax-1 or -2B does in the same assays. Co transfection assays demonstrated that Tax-ZA could efficiently transactivat e CREB-responsive promoters to the same level as Tax-1 and Tax-2B, indicati ng that the protein was functional. This report provides evidence of the fi rst functional difference between the HTLV-ZA and -2B subtypes. This compar ison of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will p rovide important insights into the mechanism of HTLV transformation.